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Sodium Channels and Neurological Disease: Insights from Scn8a Mutations in the MouseDepartment of Human Genetics, University of Michigan, Ann Arbor, Michigan, meislerm{at}umich.edu
Department of Human Genetics, University of Michigan, Ann Arbor, Michigan
Department of Human Genetics, University of Michigan, Ann Arbor, Michigan
Department of Human Genetics, University of Michigan, Ann Arbor, Michigan
Department of Human Genetics, University of Michigan, Ann Arbor, Michigan The human genome contains 10 voltage-gated sodium channel genes, 7 of which are expressed in neurons of the CNS and PNS. The availability of human genome sequences and high-throughput mutation screening methods make it likely that many human disease mutations will be identified in these genes in the near future. Mutations of Scn8a in the mouse demonstrate the broad spectrum of neurological disease that can result from different alleles of the same sodium channel gene. Null mutations of Scn8a produce motor neuron failure, loss of neuromuscular transmission, and lethal paralysis. Less severe mutations result in ataxia, tremor, muscle weakness, and dystonia. The effects of Scn8a mutations on channel properties have been studied in the Xenopusoocyte expression system and in neurons isolated from the mutant mice. The Scn8a mutations provide insight into the mode of inheritance, effect on neuronal sodium currents, and role of modifier genes in sodium channel disease, highlighting the ways in which mouse models of human mutations can be used in the future to understand the pathophysiology of human disease.
Key Words: Sodium channel • Dystonia • Epilepsy • Mouse mutant • Paralysis
The Neuroscientist, Vol. 7, No. 2,
136-145 (2001) This article has been cited by other articles:
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